https://scholars.lib.ntu.edu.tw/handle/123456789/568666
標題: | Genetic characterization of fas-associated phosphatase-1 as a putative tumor suppressor gene on chromosome 4q21.3 in hepatocellular carcinoma | 作者: | Shiou-Hwei Yeh Wu D.-C. Tsai C.-Y. Kuo T.-J. Yu W.-C. Chang Y.-S. CHI-LING CHEN Chang C.-F. Chen D.-S. PEI-JER CHEN |
公開日期: | 2006 | 出版社: | American Association for Cancer Research Inc. | 卷: | 12 | 期: | 4 | 起(迄)頁: | 1097-1108 | 來源出版物: | Clinical Cancer Research | 摘要: | Purpose: Allelic loss at chromosome 4q21-23 occurs frequently in human hepatocellular carcinoma, and the putative tumor suppressor gene (TSG) has not yet been identified. We studied the Fas-associated phosphatase-1 (FAP-1) gene as a potential candidate TSG in this region. Experimental Design: The expression level of FAP-1 RNA in hepatocellular carcinomas was evaluated by RNase protection and quantitative PCR. Sodium bisulfite modification and subsequent single-strand conformational polymorphism and sequence analyses were used to assay the methylation of CpGs at FAP-1 promoter. Direct sequencing of the FAP-1 coding region was conducted for detecting the genetic mutations. Two common single nucleotide polymorphisms of FAP-1 were selected for evaluating their association with the hepatocellular carcinoma trait in sporadic and familial hepatocellular carcinomas. Moreover, the functional effect of FAP-1 on cellular proliferation has been evaluated by small interfering RNA approach. Results: Around 50% of hepatocellular carcinomas showed significantly decreased expression of FAP-1 compared with the corresponding nontumorous liver tissues, In most cases, the RNA level was well correlated with the methylation status of promoter CpGs, suggesting that the promoter methylation may contribute to the down-regulation. Several genetic mutations of FAP-1 have been identified in hepatocellular carcinomas. The G/G genotype of FAP-1 cSNP6304 was significantly associated with the increased risk of multiplex familial hepatocellular carcinomas (odds ratio, 2.44; 95% confidence interval, 1.19-5.01). Finally, knockdown expression of FAP-1 was shown to enhance the cellular proliferation in PLC5 cells. Conclusions: FAP-1 could be inactivated during hepatocarcinogenesis, mainly attributed by allelic loss and promoter methylation. The genetic mutations and polymorphisms may also confront with the higher hepatocellular carcinoma risk. These results first suggested FAP-1 as a putative TSG in hepatocarcinogenesis. ? 2006 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984586015&doi=10.1158%2f1078-0432.CCR-05-1383&partnerID=40&md5=56cc32886923385f4840d855b9026242 https://scholars.lib.ntu.edu.tw/handle/123456789/568666 |
ISSN: | 1078-0432 | DOI: | 10.1158/1078-0432.CCR-05-1383 | SDG/關鍵字: | bisulfite; fas associated phosphatase 1; phosphatase; RNA; small interfering RNA; unclassified drug; article; cancer risk; cell proliferation; chromosome 4q; controlled study; CpG island; evaluation research; familial cancer; gene mutation; gene sequence; genotype; human; human cell; human tissue; liver carcinogenesis; liver cell carcinoma; major clinical study; methylation; nucleotide sequence; polymerase chain reaction; priority journal; protein analysis; ribonuclease protection assay; single nucleotide polymorphism; single strand conformation polymorphism; tumor suppressor gene |
顯示於: | 臨床醫學研究所 |
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